PROJECT SUMMARY/ABSTRACT Nonaromatic N-heterocycles and multicyclic alkaloids are found in numerous natural products. Tropanes, piperidines, and related nonaromatic heterocycles are also present in important pharmaceutical agents. However, current synthetic methods do not provide access to densely substituted tropane and multicyclic heterocycles. Thus, development of a synthetic strategy to access these complex chemical motifs can facilitate the search for novel pharmaceutical agents. The Ellman group has addressed this challenge by developing a C-H functionalization strategy to access complex chemical motifs. Starting from readily available and cheap precursors, Rh(I) catalyzed C-H alkenylation of ?, ?-unsaturated imines and subsequent electrocyclization with alkynes yields polysubstituted dihydropyridines. In the last couple of years, the Ellman group has also shown that silyl-substituted dihydropyridines have served as versatile building blocks that can be converted to generate azomethine ylides in situ, which undergo facile [3+2] cycloaddition to yield tropanes and related multicyclic scaffolds. This research proposal seeks to make a substantive improvement to the synthesis of densely substituted tropanes. We seek to expand the azomethine ylide chemistry to access enantiomerically pure tropanes and tropinones under organocatalytic conditions and to apply the chemistry to a natural product target. We will also generate the azomethine ylide at a new position on the dihydropyridine core to access complex [5.6] piperidine ring systems. The facile and convergent access to these complex scaffolds will establish the first example of an asymmetric approach to tropanes and tropinones from unstabilized azomethine ylides, and will also provide a convergent approach to scaffolds with the [5.6] piperidine ring system. Additionally, we seek to accomplish the first total synthesis of alstonoxine A and develop rapid access to analogues based on the spirooxindole core. Collectively, these endeavors will seek to help fill the voids in the current synthetic repertoire of complex alkaloids.